By Simon Johnson, Galit Alter, Tess Cameron, and Michael Mina
Simon Johnson is co-chair of the COVID-19 Policy Alliance and a professor at MIT’s Sloan School of Management. Galit Alter is a professor at Harvard Medical School and the Ragon Institute. Tess Cameron is a consultant and incoming principal at RA Capital. Michael Mina is a professor at Harvard T.H. Chan School of Public Health and a physician at Brigham and Women’s Hospital.
CAMBRIDGE – In Massachusetts, which has a population of close to seven million, over 6,000 people have died from COVID-19 since the beginning of March. But one relatively small group – including about 38,000 people, or 0.5% of the state’s population – accounts for 60% of these deaths. This group comprises everyone who lives in nursing homes, and protecting these people and the staff who care for them, all of whom remain highly vulnerable to severe infection, must be a top priority everywhere as economies reopen.
According to pre-pandemic data, the number of people in nursing homes typically averages around 1.3 million across the United States. These older inhabitants are cared for by a workforce that numbers around one million. Fortunately, there is now a better way to reduce significantly their risk of death: implement a focused public-health monitoring programme based on all available forms of testing – including the latest serology blood tests for antibodies – for people in and around nursing homes and the broader population.
Much emphasis has been placed on building lab capacity for polymerase chain reaction (PCR) tests, the gold standard for detecting the COVID-19 virus. PCR testing capacity is essential to manage outbreaks. In Massachusetts, heroic technological efforts by the Broad Institute of MIT and Harvard (a biomedical and genomic research organization) helped save many lives by greatly increasing the availability of testing for nursing homes and others early in the pandemic. We need more such leadership throughout the US and around the world.
PCR tests tell us if someone is currently infected – essential information to contain outbreaks – and new guidelines on nursing homes issued by the Centers for Medicare and Medicaid Services (CMS) advise that staff be tested every week, with residents to be tested weekly if any staff member or resident in the facility is positive. But, even assuming that all facilities in the US could find the test kits (swabs, test tubes, and transfer media) and processing capacity needed to comply, the monthly bill could exceed $1 billion, and many infections would not be caught early enough to prevent onward transmission. Such a strategy is unlikely to prove politically and financially sustainable. And too many people would still die.
To make the CMS nursing home guidelines and related public-health efforts more effective, states must add low-cost and easy-to-use serology tests to the mix. Serology tests measure blood samples for the presence and levels of antibodies to SARS-CoV-2, the virus that causes COVID-19. Most people who survive COVID-19 will develop antibodies, providing a window into past incidence and future risk.
But simply noting whether antibodies are present is not enough to gauge future risk. For many infections, scientists determine antibody concentrations that are deemed to protect a person from future infection. A concentration below that value means a person may be positive for antibodies but not well protected. The scientific process of finding this “threshold of protection” for any given combination of infection and antibody test is known as determining a “correlate of protection.”
For COVID-19, we are still in the early days of finding good correlates of protection, so we have not yet worked out the best threshold of protection to use. But scientists worldwide are hard at work doing just that: measuring antibodies in people who have been infected with SARS-CoV-2, stratifying them by antibody concentration, and then monitoring them for second infections. Ideally, we will find that any concentration of antibody cuts the risk of future infection. But if, as we expect, this virus acts like many other respiratory viruses we study, then antibody concentrations above a certain threshold will be correlated with greater protective immunity than concentrations below this level.
Antibody concentrations decrease over time. That’s why people can be infected with seasonal coronaviruses more than once. But can they be re-infected with SARS-CoV-2 within the same season, or perhaps only years later? The answer partly depends on how quickly protective antibodies decay.
While we can hope that COVID-19 antibodies decay very slowly (like measles antibodies, which people have for many decades), our knowledge of other coronaviruses suggests that COVID-19 antibodies may decay more swiftly, possibly after only six months or a year, like influenza. To determine the rate at which COVID-19 antibodies wane will require serological measurements from infected people over months and years.
In the meantime, we are working out what the thresholds of protection are so that quantitative antibody measurements (serology) can be reliably used to guide efficient allocation of scarce resources. To accelerate this process, hospitals, clinics, and public health programs should use quantitative rather than qualitative (positive/negative) antibody tests as much as possible, and report results directly to the public-health authorities. That way, the data can be mined to determine accurate correlates of protection that define the protective thresholds.
Pilot surveillance programmes at nursing homes in Massachusetts already combine serology and PCR testing to help facilities deploy “infection control” measures and understand risk. Ahead of any potential second wave of infection (for example, due to economic reopening or cooling weather), serology tests can help place nursing home residents into more protective social and eating groups.
Susceptible people (not previously exposed to COVID-19) would be mixed with others who have a relatively high level of antibodies, presumably representing the development of immunity to SARS-CoV-2. Surrounding susceptible people with others who can reasonably be presumed to be more resistant to disease is a long-standing and successful public health strategy for diseases such as smallpox and underpins herd immunity.
There are three reasons why serology forms the basis for all robust public-health programmes to monitor infectious disease. It generates reliable data that can readily be used to calculate the risk of future outbreaks. It is cheap (perhaps one-tenth the full cost of a PCR test). And the samples – a drop of blood on a special card – can be collected at home and transported by mail.
A number of leading companies – some of which we advise – are already using serology to monitor risk and reduce the level of danger for their workers and customers. The use of this technology is spreading fast.
Ideally, the near-real-time data from millions of blood tests – an incredible archive of the body’s response to disease – will be used to build a “weather tracking system” for infectious disease. As with meteorology, this system should track “storms” of infection around the world, helping us anticipate – and suggest appropriate action – before the next wave of COVID-19 (or another deadly pathogen) hits nursing homes and everyone else. Over time, these forecasts can become as reliable and as important as hurricane or tornado warnings today.
Once a vaccine for COVID-19 is available, how will we allocate the precious first million doses? How will we know if the vaccine protects us from reinfection in 2022? With a scaled-up serology programme, we can answer these questions and be prepared for future pathogen emergence.
Copyright: Project Syndicate, 2020.
